Vorinostat attenuates UVB-induced skin senescence by modulating NF-κB and mTOR signaling pathways
Open accessAbstract
Excessive exposure to ultraviolet B (UVB) radiation induces oxidative stress and inflammatory responses, accelerating the senescence process of skin cells. Vorinostat (SAHA), a histone deacetylase inhibitor (HDACi), is typically administered to patients with peripheral T-cell lymphoma, cutaneous T-cell lymphoma, or multiple myeloma. However, its effect on UVB-induced skin photoaging remains unclear. In this study, we used UVB to induce senescence in human immortalized keratinocyte cell line (HaCaT cells) and skin photoaging in Balb/c mice to investigate the potential of SAHA in mitigating photoaging. First, we established a UVB-induced photoaging model in HaCaT cells. We observed that UVB exposure significantly upregulated the activity of senescence-associated β-galactosidase, p16, p21, IL-1β, IL-6, and matrix metalloproteinases [collagenase (MMP-1), matrix metalloproteinase-3 (MMP-3), and gelatinase (MMP-9)]. Supplementation with SAHA effectively alleviated cellular senescence in HaCaT cells. Next, we used UVB to induce photoaging in Balb/c mouse skin. The study demonstrated that UVB markedly caused skin senescence in Balb/c mice, while SAHA effectively mitigated the changes induced by UVB irradiation. Mechanistically, we found that UVB activated the mammalian target of rapamycin (mTOR) and nuclear factor-κB (NF-κB) signaling pathways, whereas SAHA inhibited the upregulation of both mTOR and NF-κB. In summary, these findings suggest that SAHA may protect against UVB-induced cellular senescence and skin photoaging by inhibiting the mTOR and NF-κB signaling pathways. Therefore, SAHA could be a potential anti-senescence agent for mitigating skin photoaging.
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HDAC inhibitors modulate inflammatory pathways beyond transcriptional control.
“HDAC inhibitors modulate inflammatory pathways beyond transcriptional control (Dai et al., 2025).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Dai et al., 2025
The Results section (‘SAHA inhibit UVB-induced inflammatory responses in HaCaT cells’) reports reduced phosphorylated NF-κB protein after treatment with SAHA, an HDAC inhibitor. This supports modulation of inflammatory signaling beyond changes in gene expression, but the study examines one inhibitor in UVB-exposed skin cells; it does not establish the claim for HDAC inhibitors generally. (LLM, conf=0.82)
Experimental — accuracy not yet measuredHDAC inhibition can modulate NF-κB/mTOR signaling and the mitochondria-ROS-JNK-53BP1-CCF axis.
“Studies by Dai and Vizioli show that HDAC inhibition can modulate NF-κB/mTOR signaling and the mitochondria–ROS–JNK–53BP1–CCF axis (Vizioli et al., 2020; Dai et al., 2025)”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Dai et al., 2025
SAHA suppresses NF-κB/mTOR signaling and entinostat inhibits NLRP3.
“Evidence from NF-κB/mTOR suppression by SAHA and NLRP3 inhibition by entinostat illustrates the cross-tissue and cross-disease relevance of this mechanism (Dai et al., 2021; Dai et al., 2025).”
From Histone modifications and depression: epigenetic mechanisms, therapeutic targets, and translational outlook (2026) · cites this paper as Dai et al., 2025
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Lv, L.-Z., Wang, Z.-D., Ren, J.-J., Li, L.-H., Liu, X.-B., Li, J.-L., Zhu, H., Jiang, B., Han, Y.-P., Zhou, X.-M., et al. (2026) · Frontiers in Genetics · doi:10.3389/fgene.2025.1722453 · Cited by 7 · see citing works
Self-citation
- Authors
- Dai, Q., Wang, Z., Wang, X., Lian, W., Ge, Y., Song, S., Li, F., Zhao, B., Li, L., Wang, X., Zhou, M., & Cheng, J.
- Affiliations
- Dali University (CN)
- Corresponding author
- Wang, Xue
- Zhou, Min
- Cheng, Jianjie
- Venue
- Scientific Reports
- Published
- 2025-03-29
- Volume
- 15
- Issue
- 1
- Pages
- 10905-10905
- ISSN
- 2045-2322 (ISSN-L)
- PMC
- PMC11954932
- OpenAlex
- W4408966130
- Cited by
- 17
- References
- 55
- Citations by year
- 2026: 11 · 2025: 6
- FWCI
- 16.15
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- Locations
- Scientific Reports (publishedVersion, cc-by-nc-nd)
- Europe PMC (PubMed Central) (publishedVersion, cc-by-nc-nd)
- PubMed Central (publishedVersion, cc-by-nc-nd)
- PubMed (publishedVersion)
- DOAJ (DOAJ: Directory of Open Access Journals) (submittedVersion, cc-by-sa)
- Funders
- The Special Basic Cooperative Research Programs of Yunnan Provincial Undergraduate Universities’Association (202301BA070001-046)
- Topics
- Health Sciences › Medicine › Dermatology › Skin Protection and Aging
- Health Sciences › Medicine › Physiology › Telomeres, Telomerase, and Senescence
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › melanin and skin pigmentation
- Keywords
- vorinostat, histone deacetylase inhibitors, UV-B radiation, photoaging, cellular senescence, NF-κB signaling, mTOR signaling, keratinocytes, senescence-associated β-galactosidase, p16, p21, matrix metalloproteinases, oxidative stress
- MeSH terms
- Vorinostat, HaCaT Cells, Animals, Cell Line, Humans, Mice, Inbred BALB C, Skin, Ultraviolet Rays, Signal Transduction, Skin Aging, Keratinocytes, NF-kappa B, Cellular Senescence, Mice, Histone Deacetylase Inhibitors, TOR Serine-Threonine Kinases
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